Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS

NCT ID: NCT00844844

Last Updated: 2015-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2013-07-31

Brief Summary

The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adolescent patients with plasma therapy-resistant Atypical Hemolytic-Uremic Syndrome (aHUS).

Conditions

Atypical Hemolytic Uremic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eculizumab

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: DRUG

All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Interventions

Eculizumab

All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female patients from 12 and up to 18 years weighing ≥ 40 kg who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).

2. Decrease in platelet count despite at least 4 plasma therapy (PT) treatments in the 1 week immediately prior to screening.

1. Screening platelet count , < 150 x10^9/L and at least 25% lower than the average remission platelet count or

2. If remission counts not available, platelet count at onset of the current aHUS episode must be ≤75x10^9/L and platelet count at screening must be ≤ 100 x 10^9/L despite PT treatment administration of at least 4 PT treatments in the 1 week immediately prior to screening

3. Known complement regulatory protein genetic abnormality

4. Lactate dehydrogenase (LDH) level ≥ ULN unless the patient has been receiving plasma exchange and LDH at the onset of the current aHUS episode was at least the ULN. If LDH is normal at screening, other markers indicative of ongoing hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with Sponsor

5. Creatinine level ≥ ULN for age

6. Female patients of childbearing potential must be practicing an effective, reliable and medically approved contraceptive regimen during the entire duration of the study, including the follow-up period and for up to 5 months following of eculizumab treatment discontinuation.

7. Patient's parents/legal guardian must be willing and able to give written informed consent and patient must be willing to give written informed assent.

8. Able and willing to comply with study procedures.

Exclusion Criteria

1. TTP, (defined as ADAMTS-13 activity <5%) from an historical observation (prior to initiation of plasma therapy) or as tested at the screening visit by the central laboratory

2. Malignancy within 5 years of screening.

3. Typical HUS (Shiga toxin +).

4. Known HIV infection.

5. Identified drug exposure-related HUS.

6. Infection-related HUS.

7. HUS related to bone marrow transplant

8. HUS related to vitamin B12 deficiency

9. Renal function status requiring chronic dialysis

10. Patients with a confirmed diagnosis of sepsis

11. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.

12. Pregnancy or lactation.

13. Unresolved meningococcal disease.

14. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.

15. Any medical or psychological condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.

16. Patients who have received previous treatment with eculizumab

17. Patients receiving IVIG within 8 weeks or Rituximab therapy within 12 weeks of screening.

18. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors or tacrolimus are excluded unless: [1] part of an established post-transplant anti-rejection regime, [2] patient has confirmed anti-CFH antibody requiring immunosuppressive therapy, and [3] dose of such medications have been unchanged for at least 4 weeks prior to the screening period or [4] patient is experiencing an acute aHUS relapse immediately after transplant

19. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable dose for at least 4 weeks prior to the screening period or a washout period of at least 2 weeks from the last dose of ESA therapy.

20. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures beginning 4 weeks prior to screening and throughout the entire trial.

21. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients

22. Patients between ages from 12 and up to 18 years weighing < 40 kg

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Atlanta, Georgia, United States

Fort Wayne, Indiana, United States

New York, New York, United States

New York, New York, United States

Grapevine, Texas, United States

Houston, Texas, United States

Innsbruck, , Austria

Bordeaux, , France

Lyon, , France

Nantes, , France

Paris, , France

Quimper, , France

Saint-Priest-en-Jarez, , France

Tours, , France

Aachen, , Germany

Essen, , Germany

Newcastle, , United Kingdom

Countries

United States; Austria; France; Germany; United Kingdom

References

Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.

Reference Type: DERIVED

PMID: 33783815 (View on PubMed)

Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. doi: 10.1056/NEJMoa1208981.

Reference Type: DERIVED

PMID: 23738544 (View on PubMed)

Other Identifiers

BB-IND-11075

Identifier Type: -

Identifier Source: secondary_id

EudraCT Number 2008-006953-41

Identifier Type: -

Identifier Source: secondary_id

C08-002B

Identifier Type: -

Identifier Source: org_study_id